Effectiveness of combination therapy using cobra venom factor, splenectomy, and deoxyspergualin in guinea pig to rat cardiac xenografts.
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Biomedical subjects
Publications and source records attributed to H Takagi.
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The monoclonal antibody CEA 102 against carcinoembryonic antigen was produced by immunization with purified CEA, and used as a radiotracer for the imaging of colorectal cancer. CEA102 was labeled with 131I by the chloramine-T or the Iodogen method, and administered i.v. to 20 patients with liver metastases, local recurrences, and/or primary tumors. Planar scintigraphy was performed during 5 or 6 postinfusion days. Hypersensitivity reactions such as fever and chill occurred in 4 patients, but no side effects were noted after endotoxin was excluded. Overall sensitivity was 71.4% (primary tumor 4/4, liver metastasis 5/6, lymph node metastasis 1/1, local recurrence 5/10), and no false positive was observed. In the cases of local recurrences, this method was useful to distinguish postoperative fibrosis from local recurrence. These results revealed that radiolabeled CEA102 has a great potential in qualitative diagnosis of colorectal cancer.
PURPOSE: To study combination effects of radiation and hyperthermia on the in vitro cell proliferation of cultured human retinal pigment epithelial cells; to explore possible application of the combination treatment for proliferative vitreoretinopathy. METHOD: Cultured human retinal pigment epithelial cells were treated by radiation, hyperthermia, or a combination of the two. Cell proliferation was evaluated by counting the cell number and by the uptake of bromodeoxyuridine. RESULTS: X-ray irradiation of 100 cGy or 300 cGy was not effective in suppressing proliferation of the retinal pigment epithelial cells. Similarly, heat treatment at 42 degrees C or 43 degrees C for 30 min did not suppress proliferation of the retinal pigment epithelial cells. However, combination of hyperthermia at 42 degrees C for 30 min with 300 cGy irradiation suppressed cellular growth of the retinal pigment epithelial cells to 35.7% of the control as estimated by the cell counting and to 48.3% by bromodeoxyuridine uptake study. Combination treatment of 43 degrees C, 30 min hyperthermia and 300 cGy irradiation was more effective. CONCLUSIONS: A combination of low-dose radiation and mild hyperthermia is effective in the suppression of growth of cultured human retinal pigment epithelial cells, and the effects were found to be synergistic. It is expected that the synergistic effects will lower the radiation dose and also reduce the possible side effects of radiation in the treatment of proliferative vitreoretinopathy.
The changes in blood coagulation/fibrinolysis and intestinal microvasculature after acute portal vein occlusion were studied in adult mongrel dogs. All five dogs that underwent portal vein ligation with resultant portal system thrombosis died within 81-130 min following the procedure. Fibrin deposition occurred in the small-intestine mucous-membrane capillaries within 10 min after ligation. Before ligation, high levels of tissue plasminogen activator activity were noted in small vessels, mainly those of the small-intestine submucosa. However, this activity decreased significantly after portal vein ligation, suggesting progression into irreversible disseminated intravascular coagulation. After simultaneous portal vein and superior mesenteric artery occlusion, similar changes occurred, but later than with portal vein ligation alone. The five dogs who underwent this procedure died within 70-195 min. However, if portal blood was bypassed into the femoral vein through an anti-thrombogenic heparinized hydrophilic catheter, deterioration after complete portal vein ligation was not observed; the five dogs that underwent this procedure survived.
The expression of a receptor subtype for one type of excitatory amino acid agonist, t-ACPD, was examined in developing Purkinje cells of cerebellar slices. The t-ACPD-induced responses were compared with those induced by QA in current response, single cell Ca2+ imaging and changes in the miniature currents in the same preparation. It was found that t-ACPD induced a single component of inward current, and an increase in the frequency of miniature currents associated with the presence of external Ca2+, but was ineffective at mobilizing intracellular Ca2+ even in the presence of external Ca2+. The present study suggests the expression of at least two types of metabotropic receptors in the Purkinje cell region, one of which, expressed in the Purkinje cell dendrites, is highly sensitive to QA, but relatively insensitive to t-ACPD, and the other of which is a t-ACPD-sensitive receptor expressed on the presynaptic terminals of the neurons making synapses onto Purkinje cells.
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BACKGROUND: Although serum antibody to hepatitis C virus (anti-HCV) is found in many patients with hepatocellular carcinoma, the actual roles of HCV in carcinogenesis are unknown. METHODS: With reverse transcription followed by the polymerase chain reaction (RT-PCR), HCV RNA was examined in the sera and liver tissues of 16 patients with hepatocellular carcinoma who did not have hepatitis B virus markers, 13 of whom had anti-HCV. RESULTS: In the 13 patients with anti-HCV, the HCV genomic plus-strand RNA was detected more frequently in noncancerous tissues (8 patients, 61.5%) and in sera (6 patients, 46.2%) than in cancerous tissues (3 patients, 23.1%). No viral RNA was found in either sera or tissues in the three patients without anti-HCV. By using a sense primer for the RT in the RT-PCR assay, amplification was attempted of a putative complementary minus-strand RNA that is believed to reflect viral replication in the eight patients with the plus-strand RNA. The minus-strand RNA was found in the noncancerous tissues of six patients; it was not detected in the cancerous tissues. CONCLUSIONS: These results suggest that HCV can infect and replicate predominantly in noncancerous cells but rarely in tumor cells.
Overexpression of a transforming growth factor alpha (TGF-alpha) transgene induced the development of liver tumors in 69 of 93 (74%) adult male mice. To identify factors associated with oncogenesis, liver tumors from transgenic animals were characterized at the molecular level. TGF-alpha RNA transcripts were elevated in 17 of 25 (68%) liver tumors, relative to adjacent nontumorous tissue. Expression of the endogenous c-myc and insulin-like growth factor II genes was enhanced in 7 of 19 (37%) and 12 of 16 (75%) tumors, respectively. In contrast, epidermal growth factor receptor RNA levels were unchanged or reduced in all liver tumors, and mutations were not detected in either the Ha-ras or Ki-ras genes. The occurrence of liver tumors in castrated TGF-alpha transgenic mice was reduced about 7-fold, while in ovariectomized transgenic animals the incidence was increased about 6-fold. The progeny of a cross between CD1-derived TGF-alpha transgenic (MT42) and C57BL/6 mice exhibited no reduction in tumor burden (83%); however, the incidence of tumor formation in MT42 x FVB/N offspring was substantially lower (19%). We conclude that in these transgenic mice TGF-alpha promotes tumor formation and appears to play a major role in tumor progression. Moreover, other factors that may collaborate in TGF-alpha-induced hepatocarcinogenesis include c-myc, insulin-like growth factor II, sex hormones, and the genetic background upon which the transgene operates.
Expression of HLA-DR was investigated immunohistochemically in 20 cases of intrahepatic cholangiocarcinoma, as well as 9 normal livers that had been obtained at autopsy. Five of the nine normal livers had peribiliary glands that showed HLA-DR. Positive staining for HLA-DR on tumor cells was observed in 6 of 13 cases of cholangiocarcinoma of the hepatic hilus and in only 1 of 7 cases of peripheral cholangiocellular carcinoma. In cholangiocarcinomas of the hepatic hilus, the 5-year survival rate for tumors that had positive staining for HLA-DR was better than that for tumors that had negative staining. Based on these results, the presence or absence of HLA-DR on tumor cells could have a pathologic significance for intrahepatic cholangiocarcinoma.
We characterized the effects of thyrotropin-releasing hormone (TRH; 500 nM) and guanosine 5'-0-3-thiotriphosphate (GTP gamma S; 50 microM) on two types of Ca2+ currents in pituitary-hormone-secretory GH3 cells and were surprised to find marked increases in transient, low-threshold Ca2+ currents (T currents) induced by extracellularly applied TRH or intracellularly applied GTP gamma S. The effect of TRH was blocked by intracellularly applied guanosine 5'-0-2-thiodiphosphate (GDP beta S; 100 microM). The increase in the T current was found to be accompanied by a decrease in long-lasting, high-threshold Ca2+ current (L-current), in response to both TRH or GTP gamma S. These indicate that the enhancement of Ca2+ influx by TRH (500 nM) is largely conferred by T currents in GH3 cells. A reduced concentration of TRH (5 nM) still markedly increased the T current, but failed to decrease the L current. These data suggest that the augmentation of the T currents as well as depression of the L currents by TRH (500 nM), through the activation of a GTP-binding protein, may constitute an important regulatory mechanism of sustained pituitary hormone secretion in GH3 cells.
L-arginine is considered to be a precursor substance of kyotorphin (tyrosyl-arginine), a [Met5]enkephalin releaser with antinociceptive action. We examined the antinociceptive effect of L-arginine in rats. L-Arginine (300-1000 mg/kg) administered subcutaneously (s.c.) elicited antinociception (assessed by the Randall-Selitto method) in rats with a carrageenin-treated hindpaw. Naloxone (2 mg/kg s.c.) but not N-methyl-levallorphan (20 mg/kg s.c.), a peripherally selective opioid antagonist, inhibited L-arginine-induced antinociception. Intracerebroventricular administration of L-arginine (0.2-1.0 mg/rat) produced a dose-related inhibition of the carrageenin-induced hyperalgesia. Intraplantar (i.pl.) injection of L-arginine (0.5-1.0 mg/paw) also induced antinociception, which was resistant to naloxone (2 mg/kg s.c.) but was antagonized by methylene blue (0.5 mg/paw i.pl.), a guanylate cyclase inhibitor. L-Arginine (1000 mg/kg s.c.) did not inhibit edema formation in the carrageenin-treated rat hindpaw. These results suggest that systemically administered L-arginine produces mainly an antinociceptive effect mediated by central opioidergic mechanisms in rats with carrageenin-induced hyperalgesia.
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The effects of unilateral nerve transection on manganese and copper/zinc superoxide dismutase (Mn-SOD and Cu/Zn-SOD) mRNA levels in the facial nucleus were studied by in situ hybridization. An increase of Mn-SOD mRNA levels was first seen in the ipsilateral facial nucleus 12 h after axotomy, and was most pronounced at 4-7 days after this procedure; by 56 days, the increase disappeared. There was no change in Cu/Zn-SOD mRNA levels at any time after axotomy. We further confirmed, by immunohistochemistry, that the increase in Mn-SOD transcription was followed by protein synthesis. These results are suggestive of an important role for Mn-SOD in defense, regeneration and recovery responses following nerve transection.
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